Specific Aim 1: Develop a method for recording the focal EOG in response to a centrally presented light stimulus. A total of 15 healthy volunteers over the course of 1-3 study visits have participated in the study. Initial experiments to induce a dark trough before generating the light peak were shown to be highly variable. We shifted towards elimination of the dark trough in favor of generating a baseline dark amplitude during a long dark adaptation period of 40 minutes. For the light peak, we tested various stimulus sized and found that a 20o central stimulus was insufficient to generate a response from the target area, but a 40o central stimulus could produce the target response. Therefore, our current method is dark adaptation for 25 minutes, recording in the dark (to establish the baseline amplitude) for 20 minutes, then presentation of the light stimulus for 15 minutes. This method produces a recording lasting 35 minutes, which has been well-tolerated by all subjects. In order to test the response to centrally presented 40o light stimuli, volunteers were presented various central stimuli ranging from 10 to 150 cd/m2 in intensity. While 5/9 (56%) of eyes showed a light rise to 10 cd/m2, all 36 eyes tested showed light rises in response to intensities 40 cd/m2. Light peak:baseline averaged 1.370.19. Therefore, 40 cd/m2 appears to be the minimum 40 stimulus necessary and sufficient to generate a light rise. In order to test the variation in response to scattered light from central stimuli, various background intensities ranging from 0.4 cd/m2 to 1.1 cd/m2 were presented to volunteers. At the lowest background tested, participants had no or minimal light rise. The results above indicate that our method is able to measure an EOG light rise using a centrally presented 40 deg stimulus. Specific Aim 2: Testing in healthy volunteers to determine intra- and inter-session variability. We have not yet attempted to measure variability in the focal EOG response. Specific Aim 3: Examine the focal EOG in participants with macular disease. Our results from testing healthy volunteers suggests that method provides the capability to measure an EOG light rise from a centrally presented 40 deg stimulus. We then conducted proof-of-principle experiments in 6 patients with ABCA4 retinopathy who had foveal preservation with good acuity and whom had contiguous atrophy across the macular but a normal peripheral retina. We hypothesized that these patients would have a normal full-field EOG but no focal EOG, if indeed there is no light scatter from the 40 deg stimulus. Two subjects did have normal full-field EOG with no focal EOG as predicted which supports our hypothesis. However, three other patients with ABCA4 patients had a light rise with both full-field and focal EOGs. There are two possible explanations of these results: First, the level of atrophy across the macula was not sufficient to reduce the focal EOG. Second, that the apparent focal EOG light rise was caused by scattered light. Therefore, these experiments did not provide conclusive evidence that the focal EOG is being driven by the central retina without a contribution from scattered light. Therefore, we are now enrolling patients with uveal colobomas larger than 40 deg in diameter and which do not involve the fovea. These patients have a clear cut loss of retina/RPE complex with surrounding normal retina and therefore, should provide a better test of whether scattered light confounds recording of the focal EOG.